Ligand accelerated catalysis

In summary, ligands tend to diminish the affinity of the substrate for the Lewis-acid catalyst as well as the extent of activation by this catalyst, once the ternary complex is formed. Only a few examples of ligand-accelerated catalysis " have been described... 

In summary, for the most active of catalysts, the copper(II) ion, the diamine ligands that were investigated seriously hamper catalysis mainly by decreasing the efficiency of coordination of the dienophile. With exception of the somewhat deviant behaviour of N,N -dimethylethylenediamine, this conclusion also applies to catalysis by Ni" ions. Hence, significant ligand-accelerated catalysis using the diamine ligands appears not to be feasible. 

Likewise, the influence of the ligand catalyst ratio has been investigated. Increase of this ratio up to 1.75 1 resulted in a slight improvement of the enantioselectivity of the copper(L-tryptophan)-catalysed Diels-Alder reaction. Interestingly, reducing the ligand catalyst ratio from 1 1 to 0.5 1 resulted in a drop of the enantiomeric excess from 25 to 18 % instead of the expected 12.5 %. Hence, as anticipated, ligand accelerated catalysis is operative. 

Hie process was S 2 -selective in the presence of catalytic amounts of ligands fS)-32 or Is, R, Rj-43 and CufOTf )2- Hiis is another example of ligand-accelerated catalysis without the ligand tlie reaction was much slower and proceeded witli low regioselectivity. 

Lawesson s reagent 475 f., 738, 742, 746, 752 Lederle 562 lepicidin aglycon 595 f. ligand-accelerated catalysis 681 f. lignane 95... 

Yang12 has effected an intramolecular asymmetric carbonyl-ene reaction between an alkene and an a-keto ester. Reaction optimization studies were performed by changing the Lewis acid, solvent, and chiral ligand. Ligand-accelerated catalysis was observed for Sc(OTf)3, Cu(OTf)2, and Zn(OTf)2 (Equation (6)). The resulting optically active m-l-hydroxyl-2-allyl esters provide an entry into multiple natural products. 

As mentioned in Chapter 1, ligand-accelerated catalysis occurs when a more effective chiral catalyst is obtained by replacing an achiral ligand with a chiral one. Mikami et al.89 reported a different phenomenon in which a more active catalyst was formed by combining an achiral pre-catalyst with several chiral ligands. They found that the most active and enantioselective chiral catalyst was formed in preference to other possible ligand combinations (Scheme 8 43). 

As a result of the catalytic center-chiral entity interaction the reaction rate accelerates substantially. This phenomenon was described for the first time by Sharpless [6], who coined the term ligand accelerated catalysis. Unfortunately, the reasons for this phenomenon are still not well... 

About a decade after the discovery of the asymmetric epoxidation described in Chapter 14.2, another exciting discovery was reported from the laboratories of Sharpless, namely the asymmetric dihydroxylation of alkenes using osmium tetroxide. Osmium tetroxide in water by itself will slowly convert alkenes into 1,2-diols, but as discovered by Criegee [15] and pointed out by Sharpless, an amine ligand accelerates the reaction (Ligand-Accelerated Catalysis [16]), and if the amine is chiral an enantioselectivity may be brought about. 

This class of ligands produces ligand-accelerated catalysis of the 1,4-addition of diorganozinc reagents to a variety of substrates, see ref. 37. 

Sharpless et al. coined the word ligand-accelerated catalysis (LAC), which means the construction of an active chiral catalyst from an achiral precatalyst via ligand exchange with a chiral ligand. By contrast, a combinatorial library approach in which an achiral pre-catalyst combined with several chiral ligand components (L, L, —) may selectively assemble in the presence of several chiral activators (A, A, —) into the most catalytically active and enantioselective activated catalyst (ML A" ) (Scheme 8.16). ... 

Although the reaction system contains several Ti-tartrate complexes, the species containing equimolar amounts of Ti and tartrate is the most active catalyst. The reaction is much faster than Ti(IV) tetra-alkoxide alone or Ti-tartrates of other stoichiometry and exhibits selective ligand-accelerated catalysis (64). The rate is first order in substrate and oxidant and inverse second order in inhibitor alcohol, under pseudo-first-order conditions in catalyst. The crystal and molecular structures... 

The process is an interesting example of ligand-accelerated catalysis, but the only substrate reported is benzaldehyde. It is noteworthy that the less-reactive dibutylzinc is almost as effective as diethylzinc. 

Han H, Janda KD, Soluble polymer-bound ligand-accelerated catalysis Asymmetric dihydroxylation, J. Am. Chem. Soc., 118 7632-7633, 1996. 

Alkyl carbamates such as these cannot be deprotonated in the absence of sparteine or TMEDA - the reaction is truly an instance of ligand accelerated catalysis (neither can they be deprotonated by rc-BuLi or r-BuLi-(-)-sparteine). Furthermore, if the j -BuLi-H-sparteine complex is first treated with a non-deprotonatable O-isopropyl carbamate, it becomes inactive towards deprotonation of further carbamates presumably a BuLi-sparteine-carbamate complex is formed irreversibly, and we can deduce that such a complexation is the first step in the deprotonation of other alkylcarbamates.176... 

Keywords Asymmetric dihydroxylation, Osmium tetroxide, Cinchona alkaloid, Ligand-accelerated catalysis, Immobilization... 

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